Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

摘要

Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromalsupportinhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomizedphase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dosedexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma afterfailure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longerprogression-free survival and overall survival with an acceptable tolerability profile for pomalidomide +low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patientoutcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasonesignificantly prolonged progression-free survival and favored overall survival vs high-dosedexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Bothunivariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) ortype of prior treatment was a significant predictor of progression-free survival or overall survival. Nocross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving aminimal response or better to pomalidomide + low-dose dexamethasone treatment experienced asurvival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9months, respectively, as compared with 7.5 months for patients with less than minimal response). Thesedata suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care inpatients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment